Harnessing snake venom cardiotoxins for antimicrobial peptide discovery

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  Harnessing snake venom cardiotoxins for antimicrobial peptide discovery Abstract Snake venoms are a rich source of bioactive molecules with considerable potential for drug discovery. Cardiotoxins (CTXs) from cobras ( Naja spp.) are membrane-active venom proteins and promising templates for antimicrobial peptide development. Here, we combined two computational toxin-mining strategies to identify antimicrobial peptide candidates from CTXs. First, AMPA-guided sequence mining was used to detect encrypted antimicrobial regions within CTX sequences. Second, sequence alignment and consensus-sequence analysis were employed to generate peptides from a conserved CTX scaffold. Candidate peptides were prioritised using multiple machine learning- and deep learning-based antimicrobial peptide prediction tools, resulting in fourteen CTX-inspired peptides, including two modified derivatives of CTX-p5. Antimicrobial screening showed limited activity across the peptide panel, with CTX-p5 exhibiti...

Peptidomics and pharmacological profiling of Odontobuthus doriae (Buthidae) scorpion venom at the kappa opioid receptor

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Peptidomics and pharmacological profiling of Odontobuthus doriae (Buthidae) scorpion venom at the kappa opioid receptor

Abstract

Scorpion venoms are rich in bioactive peptides, many of which act on ion channels and neurotransmitter systems, yet their capacity to interact with G protein-coupled receptors (GPCRs) has been largely unexplored. Here, we profiled the venom peptides of five species in the family Buthidae and evaluated their activity at the kappa opioid receptor (KOR). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed species-specific peptide fingerprints in the mass range between 2.5 and 4 kDa, underscoring interspecies peptide toxin variation. Following pre-purification by solid-phase extraction, radioligand displacement assays demonstrated that fractions from Odontobuthus doriae bound to KOR, with Od-e (36% acetonitrile) and Od-f (45% acetonitrile) displacing ~ 35–40% of [³H]-diprenorphine. However, BRET-based functional assays demonstrated only weak receptor activation, suggesting that these peptides may function as partial agonists or antagonists rather than full agonists. Collectively, these findings highlight scorpion venoms as a previously underexplored source of opioid receptor-interacting peptides. Systematic investigation of their structural diversity and pharmacological profiles in the future may not only expand our understanding of venom evolution but also provide novel scaffolds for GPCR ligand discovery and potential analgesic development.

Abdollahnia, A., Bata, B. B., Fraunhofer, A., Hermes, J., Atashi, J., Ghassempour, A., & Gruber, C. W. (2026). Peptidomics and pharmacological profiling of Odontobuthus doriae (Buthidae) scorpion venom at the kappa opioid receptor. Scientific Reports. https://doi.org/10.1038/s41598-025-31108-9